Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl^− Channel

Several genetic strategies for inhibiting neuronal function in mice have been described, but no system that directly suppresses membrane excitability and is triggered by a systemically administered drug, has been validated in awake behaving animals. We expressed unilaterally in mouse striatum a modified heteromeric ivermectin (IVM)-gated chloride channel from C. elegans (GluClαβ), systemically administered IVM, and then assessed amphetamine-induced rotational behavior. Rotation was observed as early as 4 hr after a single intraperitoneal IVM injection (10 mg/kg), reached maximal levels by 12 hr, and was almost fully reversed by 4 days. Multiple cycles of silencing and recovery could be performed in a single animal. In striatal slice preparations from GluClαβ-expressing animals, IVM rapidly suppressed spiking. The two-subunit GluCl/IVM system permits “intersectional” strategies designed to increase the cellular specificity of silencing in transgenic animals

Explicitly correlated trial wave functions in Quantum Monte Carlo calculations of excited states of Be and Be-

We present a new form of explicitly correlated wave function whose parameters are mainly linear, to circumvent the problem of the optimization of a large number of non-linear parameters usually encountered with basis sets of explicitly correlated wave functions. With this trial wave function we succeeded in minimizing the energy instead of the variance of the local energy, as is more common in quantum Monte Carlo methods. We applied this wave function to the calculation of the energies of Be 3P (1s22p2) and Be- 4So (1s22p3) by variational and diffusion Monte Carlo methods. The results compare favorably with those obtained by different types of explicitly correlated trial wave functions already described in the literature. The energies obtained are improved with respect to the best variational ones found in literature, and within one standard deviation from the estimated non-relativistic limitsComment: 19 pages, no figures, submitted to J. Phys.

Selective Electrical Silencing of Mammalian Neurons In Vitro by the Use of Invertebrate Ligand-Gated Chloride Channels

Selectively reducing the excitability of specific neurons will (1) allow for the creation of animal models of human neurological disorders and (2) provide insight into the global function of specific sets of neurons. We focus on a combined genetic and pharmacological approach to silence neurons electrically. We express invertebrate ivermectin (IVM)-sensitive chloride channels (Caenorhabditis elegans GluCl α and β) with a Sindbis virus and then activate these channels with IVM to produce inhibition via a Cl^− conductance. We constructed a three-cistron Sindbis virus that expresses the α and β subunits of a glutamate-gated chloride channel (GluCl) along with the green fluorescent protein (EGFP) marker. Expression of the C. elegans channel does not affect the normal spike activity or GABA/glutamate postsynaptic currents of cultured embryonic day 18 hippocampal neurons. At concentrations as low as 5 nM, IVM activates a Cl^− current large enough to silence infected neurons effectively. This conductance reverses in 8 hr. These low concentrations of IVM do not potentiate GABA responses. Comparable results are observed with plasmid transfection of yellow fluorescent protein-tagged (EYFP) GluCl α and cyan fluorescent protein-tagged (ECFP) GluCl β. The present study provides an in vitromodel mimicking conditions that can be obtained in transgenic mice and in viral-mediated gene therapy. These experiments demonstrate the feasibility of using invertebrate ligand-activated Cl^− channels as an approach to modulate excitability

Herschel Observations of the W43 "mini-starburst"

Aims: To explore the infrared and radio properties of one of the closest Galactic starburst regions. Methods: Images obtained with the Herschel Space Observatory at wavelengths of 70, 160, 250, 350, and 500 microns using the PACS and SPIRE arrays are analyzed and compared with radio continuum VLA data and 8 micron images from the Spitzer Space Telescope. The morphology of the far-infrared emission is combined with radial velocity measurements of millimeter and centimeter wavelength transitions to identify features likely to be associated with the W43 complex. Results: The W43 star-forming complex is resolved into a dense cluster of protostars, infrared dark clouds, and ridges of warm dust heated by massive stars. The 4 brightest compact sources with L > 1.5 x 10^4 Lsun embedded within the Z-shaped ridge of bright dust emission in W43 remain single at 4" (0.1 pc) resolution. These objects, likely to be massive protostars or compact clusters in early stages of evolution are embedded in clumps with masses of 10^3 to 10^4 Msun, but contribute only 2% to the 3.6 x 10^6 Lsun far-IR luminosity of W43 measured in a 16 by 16 pc box. The total mass of gas derived from the far-IR dust emission inside this region is ~10^6 Msun. Cometary dust clouds, compact 6 cm radio sources, and warm dust mark the locations of older populations of massive stars. Energy release has created a cavity blowing-out below the Galactic plane. Compression of molecular gas in the plane by the older HII region near G30.684-0.260 and the bipolar structure of the resulting younger W43 HII region may have triggered the current mini-star burst.Comment: 5 pages, 3 figures, accepted for A&A Special Issu

Service provision and barriers to care for homeless people with mental health problems across 14 European capital cities

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Entrance Channel X-HF (X=Cl, Br, and I) Complexes studied by High-Resolution Infrared Laser Spectroscopy in Helium Nanodroplets

Rotationally resolved infrared spectra are reported for halogen atom - HF free radical complexes formed in helium nanodroplets. An effusive pyrolysis source is used to dope helium droplets with Cl, Br and I atoms, formed by thermal dissociation of Cl$_2$, Br$_2$ and I$_2$. A single hydrogen fluoride molecule is then added to the droplets, resulting in the formation of the X-HF complexes of interest. Analysis of the resulting spectra confirms that the observed species have $^2\Pi_{3/2}$ ground electronic states, consistent with the linear hydrogen bound structures predicted from theory. Stark spectra are also reported for these species, from which the permanent electric dipole moments are determined.Comment: 41 pages, 16 figures, 5 table

Mixed Higgsino Dark Matter from a Large SU(2) Gaugino Mass

We observe that in SUSY models with non-universal GUT scale gaugino mass parameters, raising the GUT scale SU(2) gaugino mass |M_2| from its unified value results in a smaller value of -m_{H_u}^2 at the weak scale. By the electroweak symmetry breaking conditions, this implies a reduced value of \mu^2 {\it vis \`a vis} models with gaugino mass unification. The lightest neutralino can then be mixed Higgsino dark matter with a relic density in agreement with the measured abundance of cold dark matter (DM). We explore the phenomenology of this high |M_2| DM model. The spectrum is characterized by a very large wino mass and a concomitantly large splitting between left- and right- sfermion masses. In addition, the lighter chargino and three light neutralinos are relatively light with substantial higgsino components. The higgsino content of the LSP implies large rates for direct detection of neutralino dark matter, and enhanced rates for its indirect detection relative to mSUGRA. We find that experiments at the LHC should be able to discover SUSY over the portion of parameter space where m_{\tg} \alt 2350-2750 ~GeV, depending on the squark mass, while a 1 TeV electron-positron collider has a reach comparable to that of the LHC. The dilepton mass spectrum in multi-jet + \ell^+\ell^- + \eslt events at the LHC will likely show more than one mass edge, while its shape should provide indirect evidence for the large higgsino content of the decaying neutralinos.Comment: 36 pages with 26 eps figure

Coding SNPs analysis highlights genetic relationships and evolution pattern in eggplant complexes

[EN] Brinjal (Solanum melongena), scarlet (S. aethiopicum) and gboma (S. macrocarpon) eggplants are three Old World domesticates. The genomic DNA of a collection of accessions belonging to the three cultivated species, along with a representation of various wild relatives, was characterized for the presence of single nucleotide polymorphisms (SNPs) using a genotype-by-sequencing approach. A total of 210 million useful reads were produced and were successfully aligned to the reference eggplant genome sequence. Out of the 75,399 polymorphic sites identified among the 76 entries in study, 12,859 were associated with coding sequence. A genetic relationships analysis, supported by the output of the FastSTRUCTURE software, identified four major sub-groups as present in the germplasm panel. The first of these clustered S. aethiopicum with its wild ancestor S. anguivi; the second, S. melongena, its wild progenitor S. insanum, and its relatives S. incanum, S. lichtensteinii and S. linneanum; the third, S. macrocarpon and its wild ancestor S. dasyphyllum; and the fourth, the New World species S. sisymbriifolium, S. torvum and S. elaeagnifolium. By applying a hierarchical FastSTRUCTURE analysis on partitioned data, it was also possible to resolve the ambiguous membership of the accessions of S. campylacanthum, S. violaceum, S. lidii, S. vespertilio and S. tomentsum, as well as to genetically differentiate the three species of New World Origin. A principal coordinates analysis performed both on the entire germplasm panel and also separately on the entries belonging to sub-groups revealed a clear separation among species, although not between each of the domesticates and their respective wild ancestors. There was no clear differentiation between either distinct cultivar groups or different geographical provenance. Adopting various approaches to analyze SNP variation provided support for interpretation of results. The genotyping-by-sequencing approach showed to be highly efficient for both quantifying genetic diversity and establishing genetic relationships among and within cultivated eggplants and their wild relatives. The relevance of these results to the evolution of eggplants, as well as to their genetic improvement, is discussed.This work has been funded in part by European Unions Horizon 2020 Research and Innovation Programme under grant agreement No 677379 (G2P-SOL project: Linking genetic resources, genomes and phenotypes of Solanaceous crops) and by Spanish Ministerio de Economia, Industria y Competitividad and Fondo Europeo de Desarrollo Regional (grant AGL2015-64755-R from MINECO/FEDER). Funding has also been received from the initiative "Adapting Agriculture to Climate Change: Collecting, Protecting and Preparing Crop Wild Relatives", which is supported by the Government of Norway. This last project is managed by the Global Crop Diversity Trust with the Millennium Seed Bank of the Royal Botanic Gardens, Kew and implemented in partnership with national and international gene banks and plant breeding institutes around the world. For further information see the project website:http://www.cwrdiversity.org/. Pietro Gramazio is grateful to Universitat Politecnica de Valencia for a pre-doctoral (Programa FPI de la UPV-Subprograma 1/2013 call) contract. Mariola Plazas is grateful to Spanish Ministerio de Economia, Industria y Competitividad for a post-doctoral grant within the Santiago Grisolia Programme (FCJI-2015-24835). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Acquadro, A.; Barchi, L.; Gramazio, P.; Portis, E.; Vilanova Navarro, S.; Comino, C.; Plazas Ávila, MDLO.... (2017). Coding SNPs analysis highlights genetic relationships and evolution pattern in eggplant complexes. PLoS ONE. 12(7). https://doi.org/10.1371/journal.pone.0180774Se018077412